Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Laura Baumgartner, Karin Wuertz-kozak, Christine L. Le Maitre, Francis Wignall, Stephen M. Richardson, Judith Hoyland, Carlos Ruiz Wills, Miguel A. González Ballester, Michael Neidlin, Leonidas G. Alexopoulos, Jérôme Noailly

Research output: Contribution to journalReview articlepeer-review

Abstract

Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations’ processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.
Original languageEnglish
Article number703
Pages (from-to)1-42
Number of pages42
JournalInternational Journal of Molecular Sciences
Volume22
Issue number2
Early online date12 Jan 2021
DOIs
Publication statusPublished - 12 Jan 2021

Keywords

  • Computational multiphysics
  • Computational systems biology
  • Disc cell molecular biology
  • Extracellular matrix
  • Intervertebral disc
  • Intervertebral disc degeneration
  • Multifactorial cell stimulation
  • Multiscale modeling
  • Regenerative medicine
  • Tissue Engineering/methods
  • Humans
  • Signal Transduction/physiology
  • Animals
  • Intervertebral Disc Degeneration/physiopathology
  • Computer Simulation
  • Intervertebral Disc/physiopathology
  • Extracellular Matrix/physiology

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